{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:39:45Z","timestamp":1789558785711,"version":"build-2803163510"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2018,3,6]],"date-time":"2018-03-06T00:00:00Z","timestamp":1520294400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"name":"National Cancer Center Research and Development Fund","award":["25-A-6 and 28-A-9"],"award-info":[{"award-number":["25-A-6 and 28-A-9"]}]},{"name":"Advanced Research for Medical Products Mining Programme of the National Institute of Biomedical Innovation"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cancer Res Clin Oncol"],"published-print":{"date-parts":[[2018,5]]},"DOI":"10.1007\/s00432-018-2619-3","type":"journal-article","created":{"date-parts":[[2018,3,6]],"date-time":"2018-03-06T02:21:54Z","timestamp":1520302914000},"page":"893-900","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Podoplanin-positive cancer-associated fibroblast recruitment within cancer stroma is associated with a higher number of single\u00a0nucleotide variants in cancer cells in lung adenocarcinoma"],"prefix":"10.1007","volume":"144","author":[{"given":"Shoko","family":"Nakasone","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiyo","family":"Mimaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Ichikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiju","family":"Aokage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Miyoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Sugano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motohiro","family":"Kojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Fujii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Kuwata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Ochiai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Tsuboi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Goto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuya","family":"Tsuchihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4158-0286","authenticated-orcid":false,"given":"Genichiro","family":"Ishii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,3,6]]},"reference":[{"key":"2619_CR1","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1126\/science.aag0299","volume":"354","author":"LB Alexandrov","year":"2016","unstructured":"Alexandrov LB, Ju YS, Haase K et al (2016) Mutational signatures associated with tobacco smoking in human cancer. Science 354:618\u2013622. \n                    https:\/\/doi.org\/10.1126\/science.aag0299","journal-title":"Science"},{"key":"2619_CR2","doi-asserted-by":"publisher","first-page":"4788","DOI":"10.18632\/oncotarget.2033","volume":"5","author":"JH Bavarva","year":"2014","unstructured":"Bavarva JH, Tae H, McIver L, Garner HR (2014) Nicotine and oxidative stress induced exomic variations are concordant and overrepresented in cancer-associated genes. Oncotarget 5:4788\u20134798. \n                    https:\/\/doi.org\/10.18632\/oncotarget.2033","journal-title":"Oncotarget"},{"key":"2619_CR3","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1038\/nrc2344","volume":"8","author":"RG Bristow","year":"2008","unstructured":"Bristow RG, Hill RP (2008) Hypoxia and metabolism. Hypoxia, DNA repair and genetic instability. Nat Rev Cancer 8:180\u2013192. \n                    https:\/\/doi.org\/10.1038\/nrc2344","journal-title":"Nat Rev Cancer"},{"key":"2619_CR4","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1172\/JCI59227","volume":"122","author":"MA Collins","year":"2012","unstructured":"Collins MA, Bednar F, Zhang Y et al (2012) Oncogenic Kras is required for both the initiation and maintenance of pancreatic cancer in mice. J Clin Invest 122:639\u2013653. \n                    https:\/\/doi.org\/10.1172\/JCI59227","journal-title":"J Clin Invest"},{"key":"2619_CR5","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1002\/ijc.2910560410","volume":"56","author":"MT Dimanche-Boitrel","year":"1994","unstructured":"Dimanche-Boitrel MT, Vakaet L, Pujuguet P et al (1994) In vivo and in vitro invasiveness of a rat colon-cancer cell line maintaining E-cadherin expression: an enhancing role of tumor-associated myofibroblasts. Int J Cancer 56:512\u2013521","journal-title":"Int J Cancer"},{"issue":"Suppl 17","key":"2619_CR6","doi-asserted-by":"publisher","first-page":"3069","DOI":"10.1002\/cncr.29531","volume":"121","author":"L-YY Gou","year":"2015","unstructured":"Gou L-YY, Niu F-YY, Wu Y-LL, Zhong W-ZZ (2015) Differences in driver genes between smoking-related and non-smoking-related lung cancer in the Chinese population. Cancer 121 (Suppl 17):3069\u20133079. \n                    https:\/\/doi.org\/10.1002\/cncr.29531","journal-title":"Cancer"},{"key":"2619_CR7","doi-asserted-by":"publisher","first-page":"4769","DOI":"10.1158\/0008-5472.CAN-10-3228","volume":"71","author":"A Hoshino","year":"2011","unstructured":"Hoshino A, Ishii G, Ito T et al (2011) Podoplanin-positive fibroblasts enhance lung adenocarcinoma tumor formation: podoplanin in fibroblast functions for tumor progression. Cancer Res 71:4769\u20134779. \n                    https:\/\/doi.org\/10.1158\/0008-5472.CAN-10-3228","journal-title":"Cancer Res"},{"key":"2619_CR8","doi-asserted-by":"publisher","first-page":"11345","DOI":"10.1007\/s13277-014-2450-7","volume":"35","author":"H Inoue","year":"2014","unstructured":"Inoue H, Tsuchiya H, Miyazaki Y et al (2014) Podoplanin expressing cancer-associated fibroblasts in oral cancer. Tumour Biol 35:11345\u201311352. \n                    https:\/\/doi.org\/10.1007\/s13277-014-2450-7","journal-title":"Tumour Biol"},{"key":"2619_CR9","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1378\/chest.11-2458","volume":"142","author":"M Ito","year":"2012","unstructured":"Ito M, Ishii G, Nagai K et al (2012) Prognostic impact of cancer-associated stromal cells in patients with stage I lung adenocarcinoma. Chest 142:151\u2013158. \n                    https:\/\/doi.org\/10.1378\/chest.11-2458","journal-title":"Chest"},{"key":"2619_CR10","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1038\/nrc1877","volume":"6","author":"R Kalluri","year":"2006","unstructured":"Kalluri R, Zeisberg M (2006) Fibroblasts in cancer. Nat Rev Cancer 6:392\u2013401. \n                    https:\/\/doi.org\/10.1038\/nrc1877","journal-title":"Nat Rev Cancer"},{"key":"2619_CR11","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/bmt.2012.244","volume":"48","author":"Y Kanda","year":"2013","unstructured":"Kanda Y (2013) Investigation of the freely available easy-to-use software \u201cEZR\u201d for medical statistics. Bone Marrow Transplant 48:452\u2013458. \n                    https:\/\/doi.org\/10.1038\/bmt.2012.244","journal-title":"Bone Marrow Transplant"},{"key":"2619_CR12","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1016\/j.celrep.2015.07.010","volume":"12","author":"A Kuchnio","year":"2015","unstructured":"Kuchnio A, Moens S, Bruning U et al (2015) The cancer cell oxygen sensor PHD2 promotes metastasis via activation of cancer-associated fibroblasts. Cell Rep 12:992\u20131005. \n                    https:\/\/doi.org\/10.1016\/j.celrep.2015.07.010","journal-title":"Cell Rep"},{"key":"2619_CR13","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/2041-9414-4-5","volume":"4","author":"KR Luoto","year":"2013","unstructured":"Luoto KR, Kumareswaran R, Bristow RG (2013) Tumor hypoxia as a driving force in genetic instability. Genome Integr 4:5. \n                    https:\/\/doi.org\/10.1186\/2041-9414-4-5","journal-title":"Genome Integr"},{"key":"2619_CR14","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1016\/j.bbadis.2012.10.013","volume":"1832","author":"T Marsh","year":"2013","unstructured":"Marsh T, Pietras K, McAllister SS (2013) Fibroblasts as architects of cancer pathogenesis. Biochim Biophys Acta 1832:1070\u20131078. \n                    https:\/\/doi.org\/10.1016\/j.bbadis.2012.10.013","journal-title":"Biochim Biophys Acta"},{"key":"2619_CR15","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1002\/ijc.29464","volume":"137","author":"S Neri","year":"2015","unstructured":"Neri S, Ishii G, Hashimoto H et al (2015) Podoplanin-expressing cancer-associated fibroblasts lead and enhance the local invasion of cancer cells in lung adenocarcinoma. Int J Cancer 137:784\u2013796. \n                    https:\/\/doi.org\/10.1002\/ijc.29464","journal-title":"Int J Cancer"},{"key":"2619_CR16","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1378\/chest.12-0913","volume":"143","author":"S Ono","year":"2013","unstructured":"Ono S, Ishii G, Nagai K et al (2013) Podoplanin-positive cancer-associated fibroblasts could have prognostic value independent of cancer cell phenotype in stage I lung squamous cell carcinoma: usefulness of combining analysis of both cancer cell phenotype and cancer-associated fibroblast phenotype. Chest 143:963\u2013970. \n                    https:\/\/doi.org\/10.1378\/chest.12-0913","journal-title":"Chest"},{"key":"2619_CR17","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.cell.2005.02.034","volume":"121","author":"A Orimo","year":"2005","unstructured":"Orimo A, Gupta P, Sgroi D et al (2005) Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1\/CXCL12 secretion. Cell 121:335\u2013348. \n                    https:\/\/doi.org\/10.1016\/j.cell.2005.02.034","journal-title":"Cell"},{"key":"2619_CR18","doi-asserted-by":"publisher","first-page":"7435","DOI":"10.1038\/sj.onc.1205803","volume":"21","author":"GP Pfeifer","year":"2002","unstructured":"Pfeifer GP, Denissenko MF, Olivier M et al (2002) Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers. Oncogene 21:7435\u20137451. \n                    https:\/\/doi.org\/10.1038\/sj.onc.1205803","journal-title":"Oncogene"},{"key":"2619_CR19","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1093\/carcin\/bgl257","volume":"28","author":"JE Povey","year":"2007","unstructured":"Povey JE, Darakhshan F, Robertson K et al (2007) DNA repair gene polymorphisms and genetic predisposition to cutaneous melanoma. Carcinogenesis 28:1087\u20131093. \n                    https:\/\/doi.org\/10.1093\/carcin\/bgl257","journal-title":"Carcinogenesis"},{"key":"2619_CR20","doi-asserted-by":"publisher","first-page":"2052","DOI":"10.1634\/stemcells.2007-1016","volume":"26","author":"FJ Rodr\u00edguez-Jim\u00e9nez","year":"2008","unstructured":"Rodr\u00edguez-Jim\u00e9nez FJ, Moreno-Manzano V, Lucas-Dominguez R, S\u00e1nchez-Puelles J-MM (2008) Hypoxia causes downregulation of mismatch repair system and genomic instability in stem cells. Stem Cells 26:2052\u20132062. \n                    https:\/\/doi.org\/10.1634\/stemcells.2007-1016","journal-title":"Stem Cells"},{"key":"2619_CR21","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1007\/s10549-012-1984-x","volume":"134","author":"SF Schoppmann","year":"2012","unstructured":"Schoppmann SF, Berghoff A, Dinhof C et al (2012) Podoplanin-expressing cancer-associated fibroblasts are associated with poor prognosis in invasive breast cancer. Breast Cancer Res Treat 134:237\u2013244. \n                    https:\/\/doi.org\/10.1007\/s10549-012-1984-x","journal-title":"Breast Cancer Res Treat"},{"key":"2619_CR22","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1007\/s10585-012-9549-2","volume":"30","author":"SF Schoppmann","year":"2013","unstructured":"Schoppmann SF, Jesch B, Riegler MF et al (2013) Podoplanin expressing cancer associated fibroblasts are associated with unfavourable prognosis in adenocarcinoma of the esophagus. Clin Exp Metastasis 30:441\u2013446. \n                    https:\/\/doi.org\/10.1007\/s10585-012-9549-2","journal-title":"Clin Exp Metastasis"},{"key":"2619_CR23","doi-asserted-by":"publisher","first-page":"1971","DOI":"10.3892\/or.2017.5479","volume":"37","author":"T Shan","year":"2017","unstructured":"Shan T, Chen S, Chen X et al (2017) Cancer-associated fibroblasts enhance pancreatic cancer cell invasion by remodeling the metabolic conversion mechanism. Oncol Rep 37:1971\u20131979. \n                    https:\/\/doi.org\/10.3892\/or.2017.5479","journal-title":"Oncol Rep"},{"key":"2619_CR24","doi-asserted-by":"publisher","first-page":"e73484","DOI":"10.1371\/journal.pone.0073484","volume":"8","author":"A Suzuki","year":"2013","unstructured":"Suzuki A, Mimaki S, Yamane Y et al (2013) Identification and characterization of cancer mutations in Japanese lung adenocarcinoma without sequencing of normal tissue counterparts. PLoS One 8:e73484. \n                    https:\/\/doi.org\/10.1371\/journal.pone.0073484","journal-title":"PLoS One"},{"key":"2619_CR25","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1016\/j.cell.2016.03.029","volume":"165","author":"CJ Tape","year":"2016","unstructured":"Tape CJ, Ling S, Dimitriadi M et al (2016) Oncogenic KRAS regulates tumor cell signaling via stromal reciprocation. Cell 165:910\u2013920. \n                    https:\/\/doi.org\/10.1016\/j.cell.2016.03.029","journal-title":"Cell"},{"key":"2619_CR26","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/S0027-5107(98)00042-6","volume":"400","author":"J Yuan","year":"1998","unstructured":"Yuan J, Glazer PM (1998) Mutagenesis induced by the tumor microenvironment. Mutat Res 400:439\u2013446","journal-title":"Mutat Res"},{"key":"2619_CR27","doi-asserted-by":"publisher","first-page":"9664","DOI":"10.18632\/oncotarget.1856","volume":"5","author":"J Zhang","year":"2014","unstructured":"Zhang J, Cao J, Ma S et al (2014) Tumor hypoxia enhances non-small cell lung cancer metastasis by selectively promoting macrophage M2 polarization through the activation of ERK signaling. Oncotarget 5:9664\u20139677. \n                    https:\/\/doi.org\/10.18632\/oncotarget.1856","journal-title":"Oncotarget"}],"container-title":["Journal of Cancer Research and Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00432-018-2619-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-018-2619-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-018-2619-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,3,5]],"date-time":"2019-03-05T23:10:51Z","timestamp":1551827451000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00432-018-2619-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,6]]},"references-count":27,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,5]]}},"alternative-id":["2619"],"URL":"https:\/\/doi.org\/10.1007\/s00432-018-2619-3","relation":{},"ISSN":["0171-5216","1432-1335"],"issn-type":[{"value":"0171-5216","type":"print"},{"value":"1432-1335","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,6]]},"assertion":[{"value":"3 September 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 March 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 March 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This article does not contain any studies with animals performed by any of the authors. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}